Arabinosyladenine (ARA-A) and arabinosyladenine-5'-monophosphate (ARA-AMP) are now in clinical trial here and elsewhere as antiviral-agents against herpes virus infections in severely ill patients. We have an opportunity to study the clinical pharmacokinetics and pharmacology of these agents and their metabolite, arabinosylhypoxanthine (ARA-H) in conjunction with the on-going in-depth studies of their antiviral efficacy. Our first aim is to develop optimal and precise analytical methods for measuring these compounds in plasma and urine. The second aim is to study correlations between pharmacokinetic parameters and responses to therapy, because not all patients respond to present therapeutic trial protocols and some drug toxicity has been noted. The long term aim is to find ways to adjust drug doses and dose-schedules more optimally for individual patients, by means of pharmacokinetic studies. The background and rationale for these studies can be further outlined as follows. Both ARA-A and ARA-AMP must be given intravenously, but ARA-AMP is more water soluble than ARA-A, and is therefore easier to administer by this route. Most of the clinical experience so far has been with ARA-A, but ARA-AMP is now also in trial. It is believed that ARA-AMP is rapidly converted to ARA-A in vivo, which in turn is rapidly converted to ARA-H. The latter appears to have some antiviral efficacy, but much less than ARA-A. Individual differences in the metabolism and excretion of these drugs and their end products could be one factor that determines responses to therapy. The identification of useful correlations between clinical responses and pharmacokinetic parameters of metabolism and excretion of these compounds should improve success of therapy and avoidance of toxicity by allowing more accurate selection of doses and dose-schedules for individual patients.